The present invention relates to a process for the preparation of dialkyl malonates. The terms malonates and alkyl malonates as used herein refer specifically to dialkyl malonates.
Dialkyl malonates are compounds employed as a synthesis intermediate in the preparation of many plant-protection and pharmaceutical compounds.
It is known to prepare dialkyl malonates, for example, according to the article described in Ullmann, 1960, vol. 12, p. 192, by condensing the sodium salt of monochloroacetic acid with sodium cyanide in water, followed by esterification with ethanol.
This process enables malonates to be manufactured only at a high cost and under safety conditions which are difficult to maintain. Accordingly, companies which manufacture malonates have for some years endeavored to improve the methods of preparation of malonates, especially from less costly raw materials, such as carbon monoxide.
The first process for the synthesis of malonates from ethyl chloroacetate and carbon monoxide was described in U.S. Pat. No. 3,116,306, in which a carbonylation of an alkyl halide is carried out in the presence of a cobalt tetracarbonyl salt of formula Co(CO).sub.4 M in which M denotes an alkali or alkaline-earth metal, zinc, mercury, tin or iron in the presence of an organic base such as tertiary amines or sodium and potassium alcoholates. It is stated in this text that alkali metal hydroxides may be employed, but that they react with the alkyl halide to form undesirable byproducts.
Some processes based on the above-mentioned process have been described, for example in Patent No. FR 2,253,006, where the carbonylation catalyst is cobalt carbonyl instead of the salt described in U.S. Pat. No. 3,116,306.
Patent No. FR 2,313,345 also describes a process for the preparation of malonates from chloroacetate in the presence of carbon monoxide and a catalyst containing cobalt, the reaction being carried out in a homogeneous medium and in the presence of a solution of sodium hydroxide in an alcohol. During the reaction the use of an alcoholic solution of an alkali metal hydroxide produces one mole of water per mole of chloroacetate consumed; however, in a reaction of this kind, water is normally avoided because it causes the hydrolysis of the ester groups with subsequent formation of a monoalkyl malonic acid or of an acetic ester, which greatly reduces the reaction yield. Separation of the sodium chloride formed and recycling of the catalyst are difficult.
Several patents (U.S. Pat No. 4,399,300 and GB No. 1,448,646) also describe the use of an organic base in an anhydrous medium to avoid the ester saponification phenomena. Sodium ethylate is one such organic base. The disadvantage of employing this base is primarily its cost; furthermore, the use of large quantities of ethylate destroys the malonate and the chloroacetate. As in the preceding patent, at the end of the reaction there is a precipitation of sodium chloride, which is difficult to separate from the malonate.
The present invention has made it possible to solve the problems present in the prior art. The invention makes it possible to produce dialkyl malonates from an alkyl chloroacetate under satisfactory safety conditions and at a lower cost than in the processes of the prior art; it also permits an easy separation of the salts formed and the malonate, and easy recycling of the catalyst.
The process of the present invention can prepare dialkyl malonates by carbonylation of alkyl chloroacetate in the presence of an aliphatic alcohol, a carbonyl source such as carbon monoxide and a catalyst, wherein the reaction takes place in a two-phase liquid medium.
It was not obvious to perform this reaction in a two-phase medium containing water since it was known from the prior art that the presence of water causes the hydrolysis of esters. By performing the reaction of the present invention in a two-phase medium, it is advantageously possible to employ bases which are much less costly, such as alkali metal hydroxides, and, in addition, it permits an easy separation of the salts formed during the carbonylation reaction.
The malonates prepared by the process of the present invention are preferably alkyl malonates whose alkyl chain contains one to four carbon atoms and more preferably are diethyl malonate.
The reaction of carbonylation of alkyl chloroactates may be outlined as follows. ##STR1##
The aliphatic alcohol is preferably chosen from alcohols whose alkyl chain contains one to four carbon atoms; the use of ethyl alcohol is preferred.
The catalyst for the carbonylation reaction is preferably a cobalt-based catalyst; the use of a cobalt tetracarbonyl salt is preferred.
Use of a base in the reaction of the present invention is preferred. The base (MB) is preferably chosen from organic or inorganic bases such as:
sodium ethyl malonate PA1 sodium phosphates PA1 sodium acetate; and PA1 alkali metal hydroxides. PA1 toluene PA1 xylenes PA1 alkanes PA1 cyclohexane PA1 diisopropyl ether PA1 methyl tert-butyl ether PA1 methyl isobutyl ketone PA1 alkyl chloroacetate PA1 ethyl acetate PA1 dialkyl malonate.
The use of alkali metal hydroxides is most preferred.
The two-phase liquid medium consists of an aqueous phase serving as a medium for dissolving the inorganic base and of a hydrophobic organic phase. This organic phase is preferably chosen from:
aromatic solvents such as: PA0 aliphatic solvents such as: PA0 ethers such as: PA0 ketones such as: PA0 esters such as:
It is preferable to employ molar ratios of alcohol to the reactant alkyl chloroacetate ranging from 0.1:1 to 10:1, and still more preferably an approximately stoichiometric ratio. A ratio outside these limits is not ruled out of the invention, but does not contribute any particular advantage.